Plant-derived exosomes (PDEs) are promising nanotherapeutics for improving chronic diseases, such as diabetes mellitus. Trifolium pratense (TP) is a flowering herb with potent antioxidant and antidiabetic properties. The present study aimed to explore the diabetic-healing effects of TP-derived exosomes (TPDEs) in streptozotocin (STZ)-induced diabetic rats.
Methods
TPDEs were isolated using polyethylene glycol precipitation and serial centrifugation and characterised. STZ-induced diabetic rats were treated with TPDE doses (0, 100, 200, and 400 μg/kg) for 28 days. Biochemical factors (fasting blood sugar (FBS), insulin, C-peptide, total antioxidant capacity (TAC), and nitric oxide (NO)) were evaluated in serum samples. Also, the expression of PDX1, insulin, NGN3, and SIRT1 genes in pancreas tissues was assessed using real-time PCR.
Results
TPDE treatment decreased the serum levels of FBS and NO while increasing c-peptide, insulin, and TAC levels. It also significantly enhanced the expression of insulin, PDX1, NGN3, and SIRT1 genes. TPDEs at doses of 100 to 200 μg/kg showed the most significant antidiabetic effects.
Conclusion
TPDEs significantly improved diabetes-induced alterations in serum insulin levels, antioxidant status, and pancreas-related gene expression. It can be considered a novel complementary treatment for diabetes.
{"title":"Trifolium pratense-Derived Exosome Improved Serum Biochemical Parameters and Pancreatic Genes in STZ-Induced Diabetic Rats","authors":"Amir Hossein Khazaei, Azam Bozorgi, Elham Ghanbari, Maryam Bozorgi, Mozafar Khazaei","doi":"10.1002/edm2.70103","DOIUrl":"https://doi.org/10.1002/edm2.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Plant-derived exosomes (PDEs) are promising nanotherapeutics for improving chronic diseases, such as diabetes mellitus. <i>Trifolium pratense</i> (<i>TP</i>) is a flowering herb with potent antioxidant and antidiabetic properties. The present study aimed to explore the diabetic-healing effects of <i>TP</i>-derived exosomes (<i>TPDEs</i>) in streptozotocin (STZ)-induced diabetic rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>TPDEs</i> were isolated using polyethylene glycol precipitation and serial centrifugation and characterised. STZ-induced diabetic rats were treated with <i>TPDE</i> doses (0, 100, 200, and 400 μg/kg) for 28 days. Biochemical factors (fasting blood sugar (FBS), insulin, C-peptide, total antioxidant capacity (TAC), and nitric oxide (NO)) were evaluated in serum samples. Also, the expression of <i>PDX1, insulin, NGN3</i>, and <i>SIRT1</i> genes in pancreas tissues was assessed using real-time PCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>TPDE</i> treatment decreased the serum levels of FBS and NO while increasing c-peptide, insulin, and TAC levels. It also significantly enhanced the expression of <i>insulin, PDX1, NGN3,</i> and <i>SIRT1</i> genes. <i>TPDEs</i> at doses of 100 to 200 μg/kg showed the most significant antidiabetic effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TPDEs significantly improved diabetes-induced alterations in serum insulin levels, antioxidant status, and pancreas-related gene expression. It can be considered a novel complementary treatment for diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sitraka Angelo Raharinavalona, Tafitarilova Dorland Ranjandriarison, Thierry Razanamparany, Romuald Randriamahavonjy, Andrianirina Dave Patrick Rakotomalala
Objectives
Our study aims to determine the prevalence of erectile dysfunction (ED) and its associations with atherosclerotic cardiovascular disease (ASCVD) in Malagasy patients with diabetes mellitus (DM).
Methods
This cross-sectional study was conducted over a period of 3 years at the Soavinandriana Hospital Center. Erectile function was assessed using the International Index of Erectile Function 5-item version (IIEF-5) questionnaire, with a score of less than 22 indicating ED. The presence of ASCVD was confirmed in cases where carotid atherosclerosis (CAS), lower limb arteriopathy (LLA), coronary heart disease (CHD) and/or ischaemic stroke were present.
Results
The study population included 305 patients diagnosed with diabetes mellitus (DM). The prevalence of erectile dysfunction (ED) was 73.4%. According to the bivariate analysis, the risk factors for ED were age ≥ 55 years (odds ratio [OR] 12.0 (6.34–23.4)), hypertension (OR 6.02 (3.27–11.3)), physical inactivity (OR 8.86 (4.85–16.6)), smoking (OR 2.53 (1.32–5.09)), dyslipidemia (OR 4.11 (2.33–7.32)), type 2 DM (OR 8.80 (1.53–91.0)) and diabetes duration ≥ 10 years (OR 2.24 (1.11–4.87)), renin-angiotensin-aldosterone system blockers (OR 6.27 (3.43–11.6)), calcium-channel blockers (OR 3.01 (1.69–5.48)), diuretics (OR 2.14 (1.06–4.66)) and beta-blockers (OR 4.55 (1.85–13.5)). After adjusting for age, hypertension, physical inactivity, smoking and dyslipidemia, ED was significantly associated with ASCVD (OR 1.88 (1.01–3.69)), and CAS (OR 1.89 (1.03–3.22)). Adjusting for age, type and duration of DM, ED was found to be significantly associated with ASCVD (OR 1.91 (1.01–3.58)) and CAS (OR 2.31 (1.11–4.85)). However, there was no statistically significant association between ED, LLA, CHD and ischaemic stroke.
Conclusion
ED was very common and may be a predictor of ASCVD in patients with DM, particularly CAS. Consequently, the presence of ED should prompt the search for ASCVD, and vice versa.
{"title":"Prevalence of Erectile Dysfunction in Malagasy Patients With Diabetes Mellitus and Its Associations With Atherosclerotic Cardiovascular Diseases: A Cross-Sectional Study","authors":"Sitraka Angelo Raharinavalona, Tafitarilova Dorland Ranjandriarison, Thierry Razanamparany, Romuald Randriamahavonjy, Andrianirina Dave Patrick Rakotomalala","doi":"10.1002/edm2.70098","DOIUrl":"https://doi.org/10.1002/edm2.70098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Our study aims to determine the prevalence of erectile dysfunction (ED) and its associations with atherosclerotic cardiovascular disease (ASCVD) in Malagasy patients with diabetes mellitus (DM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study was conducted over a period of 3 years at the Soavinandriana Hospital Center. Erectile function was assessed using the International Index of Erectile Function 5-item version (IIEF-5) questionnaire, with a score of less than 22 indicating ED. The presence of ASCVD was confirmed in cases where carotid atherosclerosis (CAS), lower limb arteriopathy (LLA), coronary heart disease (CHD) and/or ischaemic stroke were present.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study population included 305 patients diagnosed with diabetes mellitus (DM). The prevalence of erectile dysfunction (ED) was 73.4%. According to the bivariate analysis, the risk factors for ED were age ≥ 55 years (odds ratio [OR] 12.0 (6.34–23.4)), hypertension (OR 6.02 (3.27–11.3)), physical inactivity (OR 8.86 (4.85–16.6)), smoking (OR 2.53 (1.32–5.09)), dyslipidemia (OR 4.11 (2.33–7.32)), type 2 DM (OR 8.80 (1.53–91.0)) and diabetes duration ≥ 10 years (OR 2.24 (1.11–4.87)), renin-angiotensin-aldosterone system blockers (OR 6.27 (3.43–11.6)), calcium-channel blockers (OR 3.01 (1.69–5.48)), diuretics (OR 2.14 (1.06–4.66)) and beta-blockers (OR 4.55 (1.85–13.5)). After adjusting for age, hypertension, physical inactivity, smoking and dyslipidemia, ED was significantly associated with ASCVD (OR 1.88 (1.01–3.69)), and CAS (OR 1.89 (1.03–3.22)). Adjusting for age, type and duration of DM, ED was found to be significantly associated with ASCVD (OR 1.91 (1.01–3.58)) and CAS (OR 2.31 (1.11–4.85)). However, there was no statistically significant association between ED, LLA, CHD and ischaemic stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ED was very common and may be a predictor of ASCVD in patients with DM, particularly CAS. Consequently, the presence of ED should prompt the search for ASCVD, and vice versa.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Poorva M. Nemlekar, Katia L. Hannah, Courtney R. Green, Gregory J. Norman
Introduction
Continuous glucose monitoring (CGM) offers a detailed view of glycaemic management, potentially enhancing the effectiveness of non-insulin, anti-diabetes medications. This study aimed to evaluate whether CGM use in combination with anti-diabetes medications is associated with changes in A1c among people with type 2 diabetes not using insulin.
Materials and Methods
This was a retrospective, observational analysis of administrative claims and linked laboratory data from Optum's Clinformatics Data Mart database. The study observation period covered 01/07/2018 through 30/06/2023 with 6-month baseline and follow-up periods. CGM use in conjunction with ≥ 1 of five anti-diabetes medication classes: metformin, sulfonylureas, sodium-glucose cotransporter-2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors and/or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was required. The primary outcome was change in A1c from baseline. Linear regression models tested the main and interaction effects of CGM and each anti-diabetes medication.
Results
Overall, 52,394 CGM-naïve adults with non-insulin-treated type 2 diabetes using anti-diabetes medications were identified (4086 CGM users; 48,308 CGM non-users). CGM use was associated with a –0.45% greater A1c change among CGM users compared to CGM non-users (p < 0.0001). After adjusting for covariates, CGM users experienced greater A1c reductions vs. CGM non-users with all medications, but statistically significant interactions showed that for DPP-4 inhibitors, GLP-1 RAs and sulfonylureas, there were greater decreases in A1c for CGM users vs. CGM non-users who were taking the medication compared to CGM users vs. CGM non-users who were not taking the medication. A1c change between CGM users vs. CGM non-users did not vary by metformin or SGLT2 inhibitor use.
Discussion
The findings suggest that CGM use could augment the glycaemic benefits of anti-diabetes medications in people with non-insulin treated type 2 diabetes. These results support broader adoption of CGM.
{"title":"Exploring Combined Use of Continuous Glucose Monitoring and Anti-Diabetes Medications on Glycaemic Control for People With Type 2 Diabetes Not Using Insulin","authors":"Poorva M. Nemlekar, Katia L. Hannah, Courtney R. Green, Gregory J. Norman","doi":"10.1002/edm2.70089","DOIUrl":"https://doi.org/10.1002/edm2.70089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Continuous glucose monitoring (CGM) offers a detailed view of glycaemic management, potentially enhancing the effectiveness of non-insulin, anti-diabetes medications. This study aimed to evaluate whether CGM use in combination with anti-diabetes medications is associated with changes in A1c among people with type 2 diabetes not using insulin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This was a retrospective, observational analysis of administrative claims and linked laboratory data from Optum's Clinformatics Data Mart database. The study observation period covered 01/07/2018 through 30/06/2023 with 6-month baseline and follow-up periods. CGM use in conjunction with ≥ 1 of five anti-diabetes medication classes: metformin, sulfonylureas, sodium-glucose cotransporter-2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors and/or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was required. The primary outcome was change in A1c from baseline. Linear regression models tested the main and interaction effects of CGM and each anti-diabetes medication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 52,394 CGM-naïve adults with non-insulin-treated type 2 diabetes using anti-diabetes medications were identified (4086 CGM users; 48,308 CGM non-users). CGM use was associated with a –0.45% greater A1c change among CGM users compared to CGM non-users (<i>p</i> < 0.0001). After adjusting for covariates, CGM users experienced greater A1c reductions vs. CGM non-users with all medications, but statistically significant interactions showed that for DPP-4 inhibitors, GLP-1 RAs and sulfonylureas, there were greater decreases in A1c for CGM users vs. CGM non-users who were taking the medication compared to CGM users vs. CGM non-users who were not taking the medication. A1c change between CGM users vs. CGM non-users did not vary by metformin or SGLT2 inhibitor use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The findings suggest that CGM use could augment the glycaemic benefits of anti-diabetes medications in people with non-insulin treated type 2 diabetes. These results support broader adoption of CGM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allahdad Khan, Waseef Ullah, Moeen Ikram, Rameez Qasim, Umama Alam, Maheen Sheraz, Ayesha Khan, Kainat Kanwal, Peter Collins, Raheel Ahmed
Background
Diabetes mellitus (DM) significantly increases the risk of cerebrovascular disease (CeVD), a major cause of mortality and long-term disability. Despite improvements in healthcare, disparities in CeVD-related mortality among diabetic populations in the United States persist.
Methods
We conducted a retrospective analysis using the CDC WONDER database from 1999 to 2020 to assess mortality trends related to CeVD among adults aged ≥ 45 years with DM. Deaths were identified using ICD-10 codes I60–I69 (CeVD) and E10–E14 (DM). Age-adjusted mortality rates (AAMRs) were calculated, and trends were analysed using Joinpoint regression, stratified by age, race/ethnicity, geography, urbanisation, and place of death.
Results
A total of 689,846 CeVD-related deaths occurred in diabetic individuals. AAMR decreased from 36.9 in 1999 to 29.3 in 2020, with an average annual percentage change (AAPC) of −1.41%. However, a sharp rise was observed from 2018 to 2020 (APC 14.87%), indicating a concerning reversal in progress. The highest crude mortality rates were in the 75–84 age group, and the lowest in the 45–54 group. Black and Hispanic populations, rural residents, and those in the Southern United States had the highest mortality rates. The Northeast and Asian populations had the lowest, reflecting persistent disparities in access to care and preventive services.
Conclusion
While CeVD mortality in diabetics declined over two decades, the recent reversal highlights emerging challenges, possibly due to healthcare disruptions and socioeconomic disparities. These findings underscore the need for targeted public health interventions to address inequities and improve outcomes in high-risk populations.
{"title":"Mortality Trends and Disparities in Cerebrovascular Disease Among Diabetic Population in the United States From 1999 to 2020: A CDC WONDER Analysis","authors":"Allahdad Khan, Waseef Ullah, Moeen Ikram, Rameez Qasim, Umama Alam, Maheen Sheraz, Ayesha Khan, Kainat Kanwal, Peter Collins, Raheel Ahmed","doi":"10.1002/edm2.70091","DOIUrl":"https://doi.org/10.1002/edm2.70091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetes mellitus (DM) significantly increases the risk of cerebrovascular disease (CeVD), a major cause of mortality and long-term disability. Despite improvements in healthcare, disparities in CeVD-related mortality among diabetic populations in the United States persist.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective analysis using the CDC WONDER database from 1999 to 2020 to assess mortality trends related to CeVD among adults aged ≥ 45 years with DM. Deaths were identified using ICD-10 codes I60–I69 (CeVD) and E10–E14 (DM). Age-adjusted mortality rates (AAMRs) were calculated, and trends were analysed using Joinpoint regression, stratified by age, race/ethnicity, geography, urbanisation, and place of death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 689,846 CeVD-related deaths occurred in diabetic individuals. AAMR decreased from 36.9 in 1999 to 29.3 in 2020, with an average annual percentage change (AAPC) of −1.41%. However, a sharp rise was observed from 2018 to 2020 (APC 14.87%), indicating a concerning reversal in progress. The highest crude mortality rates were in the 75–84 age group, and the lowest in the 45–54 group. Black and Hispanic populations, rural residents, and those in the Southern United States had the highest mortality rates. The Northeast and Asian populations had the lowest, reflecting persistent disparities in access to care and preventive services.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While CeVD mortality in diabetics declined over two decades, the recent reversal highlights emerging challenges, possibly due to healthcare disruptions and socioeconomic disparities. These findings underscore the need for targeted public health interventions to address inequities and improve outcomes in high-risk populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glucotoxicity exacerbates hyperglycemia by impairing insulin secretion and sensitivity, necessitating effective interventions. Although short-term intensive insulin therapy (SIIT) mitigates glucotoxicity, the effect of combining SIIT with sodium-glucose co-transporter 2 (SGLT2) inhibitors in hospitalised type 2 diabetes mellitus (T2DM) patients with severe hyperglycemia remains unclear. Herein, we aimed to evaluate the efficacy and safety of combining SGLT2 inhibitors with basal bolus therapy (BBT) for glycemic control in hospitalised patients with T2DM.
Materials and Methods
In this randomised, open-label, single-centre trial, 35 eligible T2DM patients hospitalised for treating hyperglycemia were allocated to the BBT (n = 17) or BBT with empagliflozin (BBT + E) groups (n = 18). Patients were monitored for 7 days using flash glucose monitoring. The primary outcome was time-in-range (TIR, 70–180 mg/dL). The secondary outcomes included time-above-range (TAR), time-below-range (TBR), daily glucose levels, total daily insulin dose and ketone body concentration.
Results
The BBT + E group exhibited a significantly higher TIR from day 2, which exceeded 70% by day 5, with reduced TAR and insulin requirements. Blood glucose levels declined more rapidly in the BBT + E group, accompanied by a modest ketone elevation without severe ketoacidosis. The TBR increased marginally on day 7, primarily nocturnally; but no symptomatic hypoglycaemia occurred.
Conclusion
The addition of SGLT2 inhibitors to BBT significantly improved early glycaemic control and reduced insulin requirements without severe ketone elevation in hospitalised T2DM patients. Routine monitoring of ketone levels and careful insulin titration are critical to ensure safety.
{"title":"Evaluating Intensive Insulin Therapy With Empagliflozin in Type 2 Diabetes: A Randomised Study","authors":"Nobutoshi Fushimi, Hiroki Hachiya, Tatsuya Iwasaka, Machi Nagao, Tomoki Masamura, Kohei Higashi, Akihiro Mori","doi":"10.1002/edm2.70096","DOIUrl":"https://doi.org/10.1002/edm2.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Glucotoxicity exacerbates hyperglycemia by impairing insulin secretion and sensitivity, necessitating effective interventions. Although short-term intensive insulin therapy (SIIT) mitigates glucotoxicity, the effect of combining SIIT with sodium-glucose co-transporter 2 (SGLT2) inhibitors in hospitalised type 2 diabetes mellitus (T2DM) patients with severe hyperglycemia remains unclear. Herein, we aimed to evaluate the efficacy and safety of combining SGLT2 inhibitors with basal bolus therapy (BBT) for glycemic control in hospitalised patients with T2DM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In this randomised, open-label, single-centre trial, 35 eligible T2DM patients hospitalised for treating hyperglycemia were allocated to the BBT (<i>n</i> = 17) or BBT with empagliflozin (BBT + E) groups (<i>n</i> = 18). Patients were monitored for 7 days using flash glucose monitoring. The primary outcome was time-in-range (TIR, 70–180 mg/dL). The secondary outcomes included time-above-range (TAR), time-below-range (TBR), daily glucose levels, total daily insulin dose and ketone body concentration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The BBT + E group exhibited a significantly higher TIR from day 2, which exceeded 70% by day 5, with reduced TAR and insulin requirements. Blood glucose levels declined more rapidly in the BBT + E group, accompanied by a modest ketone elevation without severe ketoacidosis. The TBR increased marginally on day 7, primarily nocturnally; but no symptomatic hypoglycaemia occurred.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The addition of SGLT2 inhibitors to BBT significantly improved early glycaemic control and reduced insulin requirements without severe ketone elevation in hospitalised T2DM patients. Routine monitoring of ketone levels and careful insulin titration are critical to ensure safety.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The prevalence of metabolic syndrome (MetS), a cluster of metabolic abnormalities, is rising globally, particularly in the Middle East and North Africa. Gamma-glutamyl transferase (GGT) is gaining attention as a biomarker for liver function and its association with MetS and its components.
Methods
This cross-sectional study is part of the Tehran Lipid and Glucose Study (TLGS). We included 696 adolescents (347 males) aged 10–19 from the seventh examination survey (2018–2021). MetS was defined using both the International Diabetes Federation (IDF) and Cook's criteria. Serum GGT was measured, and its association as a continuous and categorical variable was assessed with MetS and its components using logistic regression, adjusting for a large set of covariates.
Results
MetS prevalence was 15.66% and 9.19% according to Cook's and IDF criteria, respectively. Higher GGT levels were significantly associated with increased MetS risk by both definitions (odds ratio [95% confidence interval] = 1.28 [1.12–1.46] and 1.30 [1.14–1.49] per 5 U/L increase, respectively) after adjusting for age, sex, smoking and family history of type 2 diabetes mellitus. This association was attenuated upon adjusting for ALT levels. GGT levels were robustly associated with high waist circumference, with odds ratios of 1.98 [1.59–2.46] and 1.71 [1.38–2.11] per 5 U/L increase, respectively, even after adjusting for alanine aminotransferase (ALT). Associations with high blood pressure (21% and 17% increased risk by IDF and Cook's criteria) and triglycerides (13% and 16% increased risk by IDF and Cook's criteria) were significant but attenuated after ALT adjustment. No significant associations were found between GGT levels and high fasting plasma glucose or low high-density lipoprotein cholesterol.
Conclusions
Elevated serum GGT is strongly associated with a higher risk of MetS and its components, particularly central obesity, in adolescents. These findings suggest that GGT is a valuable biomarker for early MetS detection.
{"title":"The Association Between Gamma-Glutamyl Transferase and Metabolic Syndrome and Its Components Among Adolescents Applying International Diabetes Federation (IDF) and Cook's Criteria","authors":"Farzad Esmaeili, Siavash Safiee, Mitra Hasheminia, Fereidoun Azizi, Maryam Tohidi, Farzad Hadaegh","doi":"10.1002/edm2.70074","DOIUrl":"https://doi.org/10.1002/edm2.70074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The prevalence of metabolic syndrome (MetS), a cluster of metabolic abnormalities, is rising globally, particularly in the Middle East and North Africa. Gamma-glutamyl transferase (GGT) is gaining attention as a biomarker for liver function and its association with MetS and its components.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study is part of the Tehran Lipid and Glucose Study (TLGS). We included 696 adolescents (347 males) aged 10–19 from the seventh examination survey (2018–2021). MetS was defined using both the International Diabetes Federation (IDF) and Cook's criteria. Serum GGT was measured, and its association as a continuous and categorical variable was assessed with MetS and its components using logistic regression, adjusting for a large set of covariates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MetS prevalence was 15.66% and 9.19% according to Cook's and IDF criteria, respectively. Higher GGT levels were significantly associated with increased MetS risk by both definitions (odds ratio [95% confidence interval] = 1.28 [1.12–1.46] and 1.30 [1.14–1.49] per 5 U/L increase, respectively) after adjusting for age, sex, smoking and family history of type 2 diabetes mellitus. This association was attenuated upon adjusting for ALT levels. GGT levels were robustly associated with high waist circumference, with odds ratios of 1.98 [1.59–2.46] and 1.71 [1.38–2.11] per 5 U/L increase, respectively, even after adjusting for alanine aminotransferase (ALT). Associations with high blood pressure (21% and 17% increased risk by IDF and Cook's criteria) and triglycerides (13% and 16% increased risk by IDF and Cook's criteria) were significant but attenuated after ALT adjustment. No significant associations were found between GGT levels and high fasting plasma glucose or low high-density lipoprotein cholesterol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Elevated serum GGT is strongly associated with a higher risk of MetS and its components, particularly central obesity, in adolescents. These findings suggest that GGT is a valuable biomarker for early MetS detection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To explore the relationship between serum high-sensitivity C-reactive protein (hs-CRP), tissue necrosis factor-α (TNF-α) and 25-Hydroxyvitamin D (25(OH) vitamin D) with albuminuria in patients with type 2 diabetes mellitus (T2D).
Methods
This was a cross-sectional study of 86 T2D patients divided into categories of with and without albuminuria based on the urine albumin-to-creatinine ratio (UACR). A 25(OH) vitamin D concentration ≤ 15 ng/mL was defined as vitamin D deficiency, within 15–30 ng/mL as vitamin D insufficiency, and > 30 ng/mL as serum 25(OH) vitamin D sufficiency. A hs-CRP level ≤ 2.5 mg/L was considered low, whereas a hs-CRP level > 2.5 mg/L was considered high. TNF-α was classified as low or high with an 8.2 pg/mL cutoff level based on receiver operating characteristic (ROC) curve analysis. P values < 0.05 were considered to be significantly associated with albuminuria.
Results
Vitamin D deficiency was significantly more commonly observed among T2D patients with albuminuria than those without albuminuria (adjusted OR = 7.34, 95% CI = 2.3–23.6, p = 0.001). Higher serum TNF-α levels (TNF-α > 8.2 pg/mL) were more frequently associated with the presence of albuminuria in T2D patients (adjusted OR = 6.77, 95% CI = 1.61–28.4; p = 0.009). Similarly, elevated serum hs-CRP levels (hs-CRP > 2.5 mg/L) were more commonly found among patients with T2D and albuminuria than in those without (adjusted OR = 4.7, 95% CI = 1.4–15.8; p = 0.012).
Conclusions
Vitamin D deficiency is a significant correlate of albuminuria in T2D patients, independent of glomerular filtration rate (GFR) and basic inflammatory markers including hs-CRP and TNF-α. Moreover, serum hs-CRP > 2.5 mg/L and TNF-α > 8.2 pg/mL were each individually associated with a significantly increased likelihood of albuminuria in T2D patients.
{"title":"Association Between Serum Vitamin D and Albuminuria in Type 2 Diabetes Independent of Inflammatory Markers and Renal Function","authors":"Parisa Farshchi, Sahar Karimpour Reyhan, Mahsa Abbaszadeh, Soghra Rabizadeh, Alireza Esteghamati, Nasim Khajavi Rad, Soheil Karimpour Reyhan, Elahe Saffari, Manouchehr Nakhjavani","doi":"10.1002/edm2.70093","DOIUrl":"https://doi.org/10.1002/edm2.70093","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>To explore the relationship between serum high-sensitivity C-reactive protein (hs-CRP), tissue necrosis factor-α (TNF-α) and 25-Hydroxyvitamin D (25(OH) vitamin D) with albuminuria in patients with type 2 diabetes mellitus (T2D).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a cross-sectional study of 86 T2D patients divided into categories of with and without albuminuria based on the urine albumin-to-creatinine ratio (UACR). A 25(OH) vitamin D concentration ≤ 15 ng/mL was defined as vitamin D deficiency, within 15–30 ng/mL as vitamin D insufficiency, and > 30 ng/mL as serum 25(OH) vitamin D sufficiency. A hs-CRP level ≤ 2.5 mg/L was considered low, whereas a hs-CRP level > 2.5 mg/L was considered high. TNF-α was classified as low or high with an 8.2 pg/mL cutoff level based on receiver operating characteristic (ROC) curve analysis. P values < 0.05 were considered to be significantly associated with albuminuria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Vitamin D deficiency was significantly more commonly observed among T2D patients with albuminuria than those without albuminuria (adjusted OR = 7.34, 95% CI = 2.3–23.6, <i>p</i> = 0.001). Higher serum TNF-α levels (TNF-α > 8.2 pg/mL) were more frequently associated with the presence of albuminuria in T2D patients (adjusted OR = 6.77, 95% CI = 1.61–28.4; <i>p =</i> 0.009). Similarly, elevated serum hs-CRP levels (hs-CRP > 2.5 mg/L) were more commonly found among patients with T2D and albuminuria than in those without (adjusted OR = 4.7, 95% CI = 1.4–15.8; <i>p =</i> 0.012).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Vitamin D deficiency is a significant correlate of albuminuria in T2D patients, independent of glomerular filtration rate (GFR) and basic inflammatory markers including hs-CRP and TNF-α. Moreover, serum hs-CRP > 2.5 mg/L and TNF-α > 8.2 pg/mL were each individually associated with a significantly increased likelihood of albuminuria in T2D patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypoxia is involved in the pathophysiology of type 2 diabetes (T2D), and oxygen therapy (hyperoxia) has been proposed for managing T2D. As a side effect, hyperoxia increases nitric oxide (NO) metabolism and decreases NO bioavailability. This study aims to investigate the effect of hyperoxia on NO synthases (NOSs), which produce NO from L-arginine and arginase, which degrades L-arginine in the soleus muscle (SM) of rats with T2D.
Methods
A combined high-fat diet and a low dose of streptozotocin (30 mg/kg) were used to induce T2D in rats. Rats with T2D were divided into four groups (n = 6/group): Control rats exposed to normoxia (Control), control rats exposed to hyperoxia (C + HOX), diabetic rats exposed to normoxia (T2D) and diabetic rats exposed to hyperoxia (T2D + HOX). The hyperoxia and the control groups received 95% and 21% oxygen for 35 days, respectively. SM was isolated at day 35, and the protein levels of endothelial NOS (eNOS), inducible NOS (iNOS), arginase, as well as tissue concentrations of lactate and NO metabolites (nitrate+nitrite = NOx) were measured.
Results
Compared to T2D, T2D + HOX rats had lower lactate concentration by 38% (p = 0.009) and NOx concentration by 23% (p = 0.011) in SM. In SM of rats with T2D, hyperoxia decreased eNOS protein by 46.2% (1.4 ± 0.13 vs. 2.6 ± 0.2 ng/mg protein, p = 0.002) and increased arginase protein by 2.3-fold (1.04 ± 0.05 vs. 0.31 ± 0.07 ng/mg protein, p < 0.001) but did not affect iNOS protein. Hyperoxia did not affect lactate concentration, eNOS and iNOS in SM of control rats but decreased NOx concentration by 25% (p = 0.003).
Conclusion
Hyperoxia decreased NO bioavailability in SM of rats with T2D; this effect was associated with decreased eNOS and increased arginase protein levels. These findings suggest that oxygen therapy in diabetic rats may decrease NO bioavailability as a potential side effect.
{"title":"The Effect of Hyperoxia on Nitric Oxide Metabolism in the Skeletal Muscle of Male Type 2 Diabetic Rats","authors":"Mahdis Mousavi, Sajad Jeddi, Reza Norouzirad, Asghar Ghasemi","doi":"10.1002/edm2.70090","DOIUrl":"https://doi.org/10.1002/edm2.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Hypoxia is involved in the pathophysiology of type 2 diabetes (T2D), and oxygen therapy (hyperoxia) has been proposed for managing T2D. As a side effect, hyperoxia increases nitric oxide (NO) metabolism and decreases NO bioavailability. This study aims to investigate the effect of hyperoxia on NO synthases (NOSs), which produce NO from <i>L</i>-arginine and arginase, which degrades <i>L</i>-arginine in the soleus muscle (SM) of rats with T2D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A combined high-fat diet and a low dose of streptozotocin (30 mg/kg) were used to induce T2D in rats. Rats with T2D were divided into four groups (<i>n</i> = 6/group): Control rats exposed to normoxia (Control), control rats exposed to hyperoxia (C + HOX), diabetic rats exposed to normoxia (T2D) and diabetic rats exposed to hyperoxia (T2D + HOX). The hyperoxia and the control groups received 95% and 21% oxygen for 35 days, respectively. SM was isolated at day 35, and the protein levels of endothelial NOS (eNOS), inducible NOS (iNOS), arginase, as well as tissue concentrations of lactate and NO metabolites (nitrate+nitrite = NOx) were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to T2D, T2D + HOX rats had lower lactate concentration by 38% (<i>p</i> = 0.009) and NOx concentration by 23% (<i>p</i> = 0.011) in SM. In SM of rats with T2D, hyperoxia decreased eNOS protein by 46.2% (1.4 ± 0.13 vs. 2.6 ± 0.2 ng/mg protein, <i>p</i> = 0.002) and increased arginase protein by 2.3-fold (1.04 ± 0.05 vs. 0.31 ± 0.07 ng/mg protein, <i>p</i> < 0.001) but did not affect iNOS protein. Hyperoxia did not affect lactate concentration, eNOS and iNOS in SM of control rats but decreased NOx concentration by 25% (<i>p</i> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Hyperoxia decreased NO bioavailability in SM of rats with T2D; this effect was associated with decreased eNOS and increased arginase protein levels. These findings suggest that oxygen therapy in diabetic rats may decrease NO bioavailability as a potential side effect.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adeel Ahmad Khan, Noor Khalil Ebrahim Jasim, Najlaa Essa A. H. Al-Mannai, Fateen Ata, Rajen Goyal, Tania Jaber
Introduction
The appropriate management strategy for patients with thyroid nodules and indeterminate cytology on fine needle aspiration (FNA) remains unclear, especially in centres where molecular testing is not available. In this retrospective study, we aimed to identify factors predicting the risk of malignancy in these patients.
Materials and Methods
This retrospective study included consecutive patients with thyroid nodules with Bethesda III/IV cytology who underwent surgical management at Hamad Medical Corporation, Qatar, between 01/01/2015 and 30/08/2023. Patients who did not undergo surgical management were excluded. We performed univariate and multivariate logistic regression analysis to assess the factors predicting the risk of malignancy in this population.
Results
Of 449 patients included in the study, the majority were females (72.2%). The mean (SD) age was 43.7 ± 10.7 years. Arab was the most common ethnicity (56.6%), followed by South-Asian (18.9%) and South-East Asian (17.8%). Sonographic features of thyroid nodules were classified as ATA very low in 0.9%, low-risk in 49.1%, intermediate-risk in 42.05% and high-risk in 7.95%. 86.2% had Bethesda III cytology and 13.8% had Bethesda IV cytology. Histopathology of thyroidectomy specimens confirmed malignancy in 179 (39.9%) patients. The malignancy rate in Bethesda III was 37.9%, while in Bethesda IV it was 51.6%. In multivariate logistic regression analysis, ATA intermediate (OR of 1.57 (1.03–2.4); p = 0.03) and high risk (OR of 3.92 (1.81–8.48); p = 0.001) sonographic patterns were predictive of malignancy.
Conclusion
In patients with indeterminate thyroid nodule cytology and in the absence of molecular markers, the ATA sonographic pattern of thyroid nodules can guide decision- making for surgical management vs. surveillance.
{"title":"Clinical Outcomes of Patients With Bethesda III or IV Cytology on Fine Needle Aspiration of Thyroid Nodules—A Retrospective Study","authors":"Adeel Ahmad Khan, Noor Khalil Ebrahim Jasim, Najlaa Essa A. H. Al-Mannai, Fateen Ata, Rajen Goyal, Tania Jaber","doi":"10.1002/edm2.70076","DOIUrl":"https://doi.org/10.1002/edm2.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The appropriate management strategy for patients with thyroid nodules and indeterminate cytology on fine needle aspiration (FNA) remains unclear, especially in centres where molecular testing is not available. In this retrospective study, we aimed to identify factors predicting the risk of malignancy in these patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This retrospective study included consecutive patients with thyroid nodules with Bethesda III/IV cytology who underwent surgical management at Hamad Medical Corporation, Qatar, between 01/01/2015 and 30/08/2023. Patients who did not undergo surgical management were excluded. We performed univariate and multivariate logistic regression analysis to assess the factors predicting the risk of malignancy in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 449 patients included in the study, the majority were females (72.2%). The mean (SD) age was 43.7 ± 10.7 years. Arab was the most common ethnicity (56.6%), followed by South-Asian (18.9%) and South-East Asian (17.8%). Sonographic features of thyroid nodules were classified as ATA very low in 0.9%, low-risk in 49.1%, intermediate-risk in 42.05% and high-risk in 7.95%. 86.2% had Bethesda III cytology and 13.8% had Bethesda IV cytology. Histopathology of thyroidectomy specimens confirmed malignancy in 179 (39.9%) patients. The malignancy rate in Bethesda III was 37.9%, while in Bethesda IV it was 51.6%. In multivariate logistic regression analysis, ATA intermediate (OR of 1.57 (1.03–2.4); <i>p</i> = 0.03) and high risk (OR of 3.92 (1.81–8.48); <i>p</i> = 0.001) sonographic patterns were predictive of malignancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In patients with indeterminate thyroid nodule cytology and in the absence of molecular markers, the ATA sonographic pattern of thyroid nodules can guide decision- making for surgical management vs. surveillance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asad Gul Rao, Sufyan Shahid, Neha Pervez, Ramsha Pervez, Raheel Ahmed
Background
Diabetes mellitus (DM) increases susceptibility to infection and worsens outcomes in sepsis, a leading cause of preventable death. However, population-level trends in sepsis-related mortality among diabetic individuals in the United States (US) remain poorly characterised, especially in the context of the COVID-19 pandemic. This study evaluates national patterns, temporal shifts, and demographic disparities in sepsis-related mortality in diabetic patients from 1999 to 2023.
Methods
We conducted a retrospective analysis using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple Cause of Death database. Sepsis-related deaths with co-listed DM were extracted for US adults between 1999 and 2023. Age-adjusted mortality rates (AAMRs) were calculated and Joinpoint regression was used to estimate annual percentage changes (APCs) and identify significant trends.
Results
A total of 483,207 sepsis-related deaths occurred in individuals with DM during the study period. AAMRs declined significantly from 1999 to 2018 (APC: −1.22; p < 0.001), reversed sharply from 2018 to 2021 (APC: +18.14; p = 0.01), and declined again through 2023 (APC: −12.25; p < 0.001). Mortality was highest among older adults (AAMR: 32.63), males (9.72 vs. 7.80 in females), and non-Hispanic Black and American Indian/Alaska Native populations (AAMRs: 17.94 and 17.92, respectively). Hispanic populations showed the steepest pandemic-era increase (APC: +22.49) and subsequent decline (APC: −20.43). Rural areas consistently had higher AAMRs than urban areas (8.77 vs. 8.27), with sharper increases during the pandemic. State-level disparities widened dramatically from 2021 to 2023, and regionally, the South and Midwest exhibited the highest and most persistent mortality burdens.
Conclusion
Sepsis-related mortality in diabetic individuals in the US has undergone dynamic shifts over the past 25 years, punctuated by COVID-19 era surges and shaped by deep-rooted demographic, geographic, and structural inequities. These findings warrant integrated diabetes-infection care models, early sepsis recognition, and equity-driven interventions to reduce mortality.
{"title":"Trends and Disparities in Mortality due to Diabetes Mellitus and Sepsis in the US Adults: 1999–2023","authors":"Asad Gul Rao, Sufyan Shahid, Neha Pervez, Ramsha Pervez, Raheel Ahmed","doi":"10.1002/edm2.70082","DOIUrl":"https://doi.org/10.1002/edm2.70082","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetes mellitus (DM) increases susceptibility to infection and worsens outcomes in sepsis, a leading cause of preventable death. However, population-level trends in sepsis-related mortality among diabetic individuals in the United States (US) remain poorly characterised, especially in the context of the COVID-19 pandemic. This study evaluates national patterns, temporal shifts, and demographic disparities in sepsis-related mortality in diabetic patients from 1999 to 2023.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective analysis using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple Cause of Death database. Sepsis-related deaths with co-listed DM were extracted for US adults between 1999 and 2023. Age-adjusted mortality rates (AAMRs) were calculated and Joinpoint regression was used to estimate annual percentage changes (APCs) and identify significant trends.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 483,207 sepsis-related deaths occurred in individuals with DM during the study period. AAMRs declined significantly from 1999 to 2018 (APC: −1.22; <i>p</i> < 0.001), reversed sharply from 2018 to 2021 (APC: +18.14; <i>p</i> = 0.01), and declined again through 2023 (APC: −12.25; <i>p</i> < 0.001). Mortality was highest among older adults (AAMR: 32.63), males (9.72 vs. 7.80 in females), and non-Hispanic Black and American Indian/Alaska Native populations (AAMRs: 17.94 and 17.92, respectively). Hispanic populations showed the steepest pandemic-era increase (APC: +22.49) and subsequent decline (APC: −20.43). Rural areas consistently had higher AAMRs than urban areas (8.77 vs. 8.27), with sharper increases during the pandemic. State-level disparities widened dramatically from 2021 to 2023, and regionally, the South and Midwest exhibited the highest and most persistent mortality burdens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Sepsis-related mortality in diabetic individuals in the US has undergone dynamic shifts over the past 25 years, punctuated by COVID-19 era surges and shaped by deep-rooted demographic, geographic, and structural inequities. These findings warrant integrated diabetes-infection care models, early sepsis recognition, and equity-driven interventions to reduce mortality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"8 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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